COMPUTER SIMULATION METHOD FOR CALCULATING FREE ENERGY

测定多肽和蛋白质的生物活性，以 在很大程度上，是由它们的空间结构决定的。因此，计算 自由能F很重要，因为最小F是 构象稳定性。然而，使用通常的模拟 F的工艺计算比较困难。“地方州方法” Meirovitch建议的是一种使人能够提取F的程序 来自计算机模拟样本；它独立于其他 技术(如热力学积分方法)，并具有 优点如下：1)该方法适用于任何链条 灵活性、稳定状态以及随机卷曲或状态 这两种极端情况的混合，以及2)它可以用来获得 两个结构差异很大的状态之间的差值。这个 局域态方法已成功地应用于晶格模型 和一个现实的十甘氨酸连续模型。我们的短期计划 目标(第一阶段)是将该方法扩展到分子动力学样品 在水中含有侧链的线状和环状多肽。我们会 环肽(Ala-Pro-D-Phe)2在真空和真空条件下的研究 水中呈螺旋状和发夹状结晶的十丙氨酸和 神经肽促性腺激素释放激素(GnRH)。《长河》 学期目标是进一步将局域态方法扩展到更大的 诸如蛋白质-配体复合体等体系和一般问题 蛋白质折叠。这一重要的费用将被添加到洞察力- 发现Biosym Technologies，Inc.的软件包。

The biological activity of polypeptides and proteins is determined, to a large extent, by their spatial structure. Therefore, calculation of the free energy F is important since minimum F is the criterion for conformational stability. However, with the usual simulation techniques calculation of F is difficult. The "local states method" suggested by Meirovitch is a procedure which enables one to extract F from computer simulation samples; it is independent of other techniques (such as thermodynamic integration methods) and has the following advantages: 1) The method can be applied to any chain flexibility, stable states as well the random coil or states which are mixtures of these two extreme cases, and 2) It can be used to obtain deltaF between two states with a large structural difference. The local states method has been successfully applied to lattice models and to a realistic continuum model of decaglycine. Our short term goal (Phase I) is to extend the method to molecular dynamics samples of linear and cyclic peptides with side chains in water. We shall study the cyclic peptide (Ala-Pro-D-Phe)2 in vacuum and in the crystal, decaalanine in water, in both helical and hairpin states and the neuro peptide gonadotropin releasing hormone (GnRH). The long term goal is to further extend the local states method to larger systems such as protein-ligand complexes and to general problems of protein folding. This important toll will be added to the Insight- Discover software package of Biosym Technologies, Inc.